Mercapto-substituted pyridine compounds, aminocarbonyl-substituted pyridinesulfinic acid compounds and process for preparing the same

ABSTRACT

An aminocarbonyl-substituted pyridinesulfinic acid intermediate for production of an herbicide having formula (V): ##STR1## wherein R 3  and R 4  are selected from the group consisting of hydrogen and alkyl groups, or a salt thereof. The aminocarbonyl-substituted pyridinesulfinic acid or salt thereof is useful as the precursor of aminosulfonyl-substituted pyridinecarbonic acid amide, which in turn is useful as the starting material for agricultural chemicals, medicine, etc.

This is a divisional of application Ser. No. 07/471,337 filed Jan. 29,1990, which is a continuation-in-part of application Ser. Nos.07/389,647 field Aug. 4, 1989 and 07/217,021 filed Jul. 11, 1988, bothabandoned.

FIELD OF THE INVENTION

The present invention relates to novel mercapto-substituted pyridinecompound and salts thereof, and to a process for preparing the same.

The present invention also relates to novel aminocarbonyl-substitutedpyridinesulfinic acid (hereinafter referred to as ACPS), or saltsthereof as a precursor of an aminosulfonyl-substitutedpyridinecarboxylic acid amide compound (hereinafter referred to as APCA)useful as the starting material of agricultural chemicals, medicines,and the like, and to an industrially advantageous process for preparingthe same.

BACKGROUND OF THE INVENTION

The mercapto-substituted pyridine compound of the present invention ischaracterized by having an aminocarbonyl group on the pyridine ring,said aminocarbonyl group being substituted by two alkyl groups. Certainsubstituted pyridine compounds are disclosed in the respectivespecifications of U.S. Pat. No. 3,759,932; U.S. Pat. No. 4 435,206: U.S.Pat. No. 4,518,776 and U.S. Pat. No. 4,521,597. However, the abovespecifications fail to disclose the aforementioned mercapto-substitutedpyridine compound on the pyridine ring. Also U.S. Pat. No. 4,548,942discloses 2-mercaptonicotinamides represented by formula (4) in column7. These compounds are useful for preparing derivatives of(5,4b)-isothiazolo pyridine-3-one as an anti-acne agent. The patentedcompounds do not chemically overlap with those of the present invention,the aminocarbonyl group being substituted by only one alkyl group, andthe disclosed utility is quite different from the present invention.

European Patent Application Laid-Open Nos. 237,292 and 232,067 disclosea process for preparing APCA. However, the process disclosed therein isnot always satisfactory industrially because of low yield, increasedreaction steps, necessity of isolation in respective reaction steps, orof using reactants which are difficult to handle and expensive. Thepresent inventors made various studies in order to find an industriallyadvantageous process for preparing APCA and, as a result, found out thata process by way of ACPS or salts thereof according to the presentinvention is capable of providing the intended effects to complete thepresent invention.

SUMMARY OF THE INVENTION

The present invention provides a mercapto-substituted pyridine compoundhaving the general formula (I): ##STR2## where R₁ and R₂ are alkylgroups, and n is 0 or 1, and salts thereof.

The alkyl groups in R₁ and R₂ of the general formula (I) include thosehaving 1 to 6 carbon atoms, for example, methyl group, ethyl group,propyl group, butyl group and the like.

The salt of the mercapto-substituted pyridine compound includes acidaddition salts, alkali metal salts and the like, and specificallyincludes salts of the mercapto-substituted pyridine compounds of thegeneral formula (I) where n is 0, with an alkali metal such as lithium,sodium, potassium or the like.

Among the mercapto-substituted pyridine compounds and salts thereof, thecompounds having the general formula (I'): ##STR3## where R₁ ' and R₂ 'are alkyl groups and n is as defined above, and salts thereof arepreferred, and further such a combination that R₁ ' is a methyl groupand R₂ ' is a methyl group in the general formula (I'), is morepreferred.

The present invention also provides an aminocarbonylsubstitutedpyridinesulfinic acid having the general formula (V): ##STR4## where R₃and R₄ are hydrogen atoms or alkyl groups as defined above,respectively, or salts thereof. Examples of the salts of formula (V)include salts of alkali metal or alkaline earth metal such as lithium,sodium, potassium, magnesium, calcium and the like; amine salts due toamines substituted with hydrocarbon group such as triethylamine,dimethylamine and the like; quaternary ammonium salts such as ammoniumsalt due to ammonia and the like; and the like.

Of the above ACPS or salts thereof, a compound having the generalformula (V"): ##STR5## where R₃ and R₄ are as defined above, or saltsthereof are preferred, and such a combination that R₃ is hydrogen atomor methyl group and R. is methyl group in the general formula (V"), ismore preferred. Of the above ACPS or salts thereof, the salts arepreferred. Of the salts, alkali metal salts and ammonium salts arepreferred, and sodium is more preferred.

The mercapto-substituted pyridine compound of the present invention maybe prepared, as shown by the following equation: ##STR6## where M isalkali metal, x is 2 to 8, Haλ is halogen atom, and R₁, R₂, and n are asdefined above, by a synthetic reaction of pyridinepolysulfide in which ahalogeno-substituted pyridine compound having the general formula (II)is reacted with a polysulfide having the general formula (III) followedby an acid treatment.

The above ACPS or salts thereof according to the present invention maybe prepared by the following process: ##STR7## where R₃ and R₄ are asdefined above.

DETAILED DESCRIPTION OF THE INVENTION A. Mercapto-Substituted PyridineCompounds 1. Preparation of the Halogeno-Substituted Pyridine Compound

The halogeno-substituted pyridine compound may be easily prepared, forexample, by reacting thionyl chloride with a halogenopicolinic acid orhalogenonicotinic acid or halogenoisonicotinic acid followed by reactingwith amines in a solvent such as methylene chloride. Among thehalogeno-substituted pyridine compounds, such ones that the halogen atomlocated at 2, 4 or 6 position of the pyridine ring are desirable, andthe halogen atom therein is desirably chlorine atom or bromine atom.

Among the compounds of the general formula (II). N-oxide compounds mayusually be prepared by dissolving the halogeno-substituted pyridinecompound in a solvent such as water, alcohols, ethers, esters, nitriles,aliphatic hydrocarbons unsubstituted or substituted by halogen atom,fatty acids unsubstituted or substituted by halogen atom and aromatichydrocarbons, preferably water and fatty acid unsubstituted orsubstituted by halogen atom to be reacted with a peroxide. The amount ofthe solvent used is normally 10 to 10.000% by weight based on thehalogeno-substituted pyridine compound. The peroxide includes organicperacids such as perbenzoic acid, metachloroperbenzoic acid,monoperoxyphthalic acid, performic acid, peracetic acid ortrifluoroperacetic acid, organic peracid esters such as tert-butylperacetate or tert-butyl perbenzoate, alkylhydroperoxides such astert-butyl-hydroperoxide or tertamylhydroperoxide, or hydrogen peroxide,preferably performic acid, peracetic acid, trifluoroperacetic acid orhydrogen peroxide. The amount of the peroxide used is 1 to 10 moles,preferably 2 to 5 moles per one mole of the halogeno-substitutedpyridine compound. The reaction temperature is normally 0 to 120° C.,preferably 30 to 100° C. and the reaction time is generally 1 to 10hours.

2. Synthetic Reaction of Pyridinepolysulfide

The polysulfide used may include those obtained beforehand by reacting 1to 7 moles, desirably 1 to 2 moles of sulfur with one mole of a mixtureof an alkali metal hydroxide and a hydrosulfide thereof, or with onemole of an alkali metal sulfide according to the conventional process,and may also include those formed in the reaction system by reacting theabove reactants in the presence of the halogeno-substituted pyridinecompound of the general formula (II) to be directly used in situ. Thealkali metal used in the alkali metal hydroxide, the hydrosulfidethereof or the sulfide thereof may include lithium, sodium andpotassium, preferably sodium. The amount to be used of the hydroxide,hydrosulfide or sulfide is 0.75 to 5 moles, desirably 1 to 1.5 moles,respectively, per one mole of the halogenosubstituted pyridine compound.Normally water may be used as a solvent in the above reaction, but anorganic solvent miscible with polysulfide and water may also be used.Examples of the organic solvent may include lower alcohol such asmethanol, ethanol and propanol, polyalcohol such as ethylene glycol orpropylene glycol, ethers such as tetrahydrofuran, an aprotic polarsolvent such as dioxane or dimethylsulfoxide, ketones such as methylethyl ketone, nitriles such as acetonitrile, and the like. The amount ofthe solvent used is normally 10 to 1000% by weight, desirably 10 to 100%by weight based on the halogeno-substituted pyridine compound. Otherreaction conditions of the above reaction may not be generally defined,but the reaction temperature is normally 0° C. to reflux temperature,desirably 80 to 150° C. the reaction pressure is atmospheric pressure toseveral atoms, and the reaction time is generally 0.5 to 30 hours.

3. Acid Treatment

Since according to the above reaction, the mercapto-substituted pyridinecompound is usually formed as an alkali metal salt of polysulfide,application of the conventional acid treatment to the reaction productresults in liberating the intended mercapto-substituted pyridinecompound, generating hydrogen sulfide gas, and in forming sulfur. Theacid treatment is carried out, for example, by adding a non-oxidativemineral acid such as a concentrated hydrochloric acid or a dilutesulfuric acid to the reaction product in such an amount that the pHtherein becomes 3 or lower, followed by subjecting to the conventionalpurification and separation procedure, resulting in making it possibleto isolate the intended mercapto-substituted pyridine compound.

Typical examples of the mercapto-substituted pyridine compound havingthe general formula (I) and salts thereof are shown as follows:

Compound No. 1: N,N-dimethyl-2-mercaptonicotin-amide, m.p. 214-215° C.

Compound No. 2: sodium salt of N,N-dimethyl-2-mercaptonicotinamide, m.p.267-271° C.

Compound No. 3: N,N-dimethyl-2-mercaptonicotin-amide-1-oxide, m.p.115.5-118° C.

Compound No. 4: N,N-diethyl-2-mercapto-nicotinamide m.p. 207-210° C.

Compound No. 5: sodium salt of N,N-diethyl-2-mercaptonicotinamide

Compound No. 6: N,N-diethyl-2-mercaptonicotin-amide-1-oxide

Compound No. 7: 4-(N,N-dimethylaminocarbonyl)-2-mercapto-pyridine

Application of the above mercapto-substituted pyridine compound andsalts thereof to oxidation and halogenation reaction results inobtaining halogenosulfonyl-substituted pyridine compound.

The oxidation and halogenation process may include a process in whichthe mercapto-substituted pyridine compound and salts thereof are reactedwith a halogenating agent such as chlorine gas, bromine or the like inthe presence of water, an aqueous hydrochloric acid solution, aceticacid or an aqueous acetic acid solution, a process in which themercapto-substituted pyridine compound and salts thereof are reactedwith hypochlorite or hypobromite in the presence of water or an aqueoushydrochloric acid solution, and the like, the former being desirable.

In the above processes, an aprotic organic solvent may be used to makesimple the post treatment of the reaction. Examples of the solvent usedinclude benzene, hexane, toluene, xylene, methylene chloride,chloroform, carbon tetrachloride, ethylene dichloride,trichloroethylene, diethyl ether, ethyl acetate and the like. The amountof solvent used is normally 50 to 2000% by weight based on thehalogeno-substituted pyridine compound.

In the above processes, the amount of chlorine, bromine, hypochlorite,hypobromite and the like is in the range of from a theoretical amountfor reaction to such an amount as to slightly exceeding the theoreticalamount based on the mercapto-substituted pyridine compound and saltsthereof. Similarly thereto, the amount of water, the aqueoushydrochloric acid solution, acetic acid, the aqueous acetic acidsolution or the like is 50 to 2000% by weight. The aqueous hydrochloricacid solution or the aqueous acetic acid solution may be used at aconcentration of 1 to 30% by weight. In the above processes, otherreaction conditions are not generally defined, but the reactiontemperature is normally -20 to +50° C. desirably -10 to +10° C., and thereaction time is 0.1 to 5 hours. Application of the conventionalpurification and separation procedures to the reaction product resultsin making it possible to separate halogenosulfonyl-substituted pyridinecompound.

Typical examples of the halogenosulfonyl-substituted pyridine compoundare shown as follows:

Compound No. A: 2-chlorosulfonyl-N,N-dimethylnicotinamide. m.p. 114-117°C.

Compound No. B: 2-bromosulfonyl-N,N-dimethyl-nicotinamide. m.p. 108-111°C.

Compound No. C: 2-chlorosulfonyl-N,N-diethyl-nicotinamide, oilysubstance

Compound No. D: 2-bromosulfonyl-N,N-diethyl-nicotinamide

Compound No. E: 2-chlorosulfonyl-N,N-dimethyl-nicotinamide-1-oxide. m.p.96.5-100° C.

Reaction of the halogenosulfonyl-substituted pyridine compound withammonia gas or ammonia water at -10 to -100° C. leads toaminosulfonyl-substituted pyridine compound, a further reaction of whichwith 2-isocyanate-4,6-dimethoxypyrimidine or2-chlorocarbonylamino-4,6-dimethoxy-pyrimidine at -10 to +100° C. easilyleads toN-[(4,6-dimethoxypyrimidine-2-yl)aminocarbonyl]-3-aminocarboxyl-2-pyridinesulfonamide compound. Application of the pyridine sulfonamide compoundin an amount of 0.1 to 100 g per one are makes it possible toeffectively control various kinds of harmful weeds and it has such highsafety for corn as to be useful as a herbicide for the corn field.

B. ACPS Compounds

The salt formation reaction and the oxidation reaction for preparationof ACPS compounds are explained in detail below.

1. Salt Formation Reaction

The salt formation reaction is normally carried out by reacting amercapto-substituted pyridinecarboxylic acid amide compound having thegeneral formula (V) (hereinafter referred to as MPCA) with asalt-forming substance in the presence of a solvent such as water. Theamount of the solvent used is 100 to 1000% by weight relative to theweight of MPCA. Examples of the salt-forming substance includehydroxides or carbonates of alkali metal or alkaline earth metal such aslithium, sodium, potassium. magnesium, calcium and the like; amine suchas triethylamine, dimethylamine or the like; ammonia such as aqueousammonia solution, ammonia gas or the like; and the like, sodiumhydroxide and ammonia being preferred. The amount of the salt-formingsubstance used is a reacting equivalent or more relative to MPCA. forexample, 1 to 2 moles when the alkali metal salts are used, or 4 to 20moles when ammonia is used, per one mole of MPCA respectively.

The reaction temperature may not be generally defined, but is normally 0to 50° C., and the reaction time is generally 5 to 60 minutes.

The reaction product may be subjected to the conventional purificationand separation procedures to obtain the intended salts of MPCA, or maybe used for the following oxidation reaction as it is.

2. Oxidation Reaction

The oxidation reaction is carried out by dissolving or suspending thesalt of MPCA in a solvent such as water followed by dropping thereintohydrogen peroxide, or is carried out by dropping hydrogen peroxide intothe reaction product obtained from the above salt formation reaction.The concentration of hydrogen peroxide is not specifically limited, butmay be normally about 30% by weight, and its amount to be used isnormally 1.8 to 3 moles per one mole of the salt of MPCA. The reactiontemperature is not to be generally defined but is normally 0 to 100° C.,and the reaction time is generally 10 to 60 minutes.

The reaction product may be subjected to the conventional purificationand separation procedures as in the case of the above salt formationreaction to isolate the salt of ACPS, neutralization of which makes itpossible to obtain ACPS.

The ACPS or salts thereof, which are obtained by the above reaction, mayeasily be lead to APCA by amination reaction or by oxidationcondensation reaction as described below.

In an industrial practice, the salt of ACPS, which is obtained by theabove reaction, may be subjected to amination reaction or to oxidation,condensation reaction as described below, in situ without beingisolated. In the above case, the salt of ACPS. which is applicable tooxidation, condensation reaction, is limited to ammonium salt, when asalt other than ammonium salt of ACPS is formed, it is once convertedinto ammonium salt by salt conversion reaction. The salt conversionreaction is explained below.

3. Salt Conversion Reaction

The salt conversion reaction is carried out by dissolving or suspendingalkali metal salts, alkaline earth metal salts or amine salts of ACPS ina solvent such as water followed by generally adding ammonia andsubsequently an acid, or is carried out by generally adding ammonia andsubsequently an acid to the reaction product containing the alkali metalsalt, alkaline earth metal salt, or amine salt of ACPS, which has beenobtained according to the above oxidation reaction. Specific examples ofthe ammonia used include an aqueous ammonia solution, ammonia gas andthe like. The amount of the ammonia used is normally 4 to 20 moles perone mole of the alkali metal salt, alkaline earth metal salt or aminesalt of ACPS. Examples of the acid include inorganic acid or organicacid such as sulfuric acid, hydrochloric acid nitric acid, phosphoricacid, acetic acid and the like, sulfuric acid being preferred. Theamount of the acid used is 1 to 4 moles per one mole of the alkali metalsalt. alkaline earth metal salt or amine salt of the above ACPS. Thereaction temperature is not generally defined, but is normally 0 to 50°C. and the reaction time is generally 10 to 60 minutes.

The reaction product may be subjected to the conventional purificationand separation procedures to isolate ammonium salt of ACPS, but may beapplicable to oxidation, concentration reaction, which is explainedbelow, as it is in the same manner as in the case of the above reaction.

The ACPS or alkali metal salts thereof in the second embodiment of thepresent invention may also be prepared according to the followingalternate process: ##STR8## wherein R₃ and R₄ are as defined above, M'is an alkali metal element, x is 2 to 8, and y is 1 to 8.

The above polysulfidation reaction and oxidation reaction will beexplained in detail.

4. Polysulfidation Reaction

On polysulfidation reaction, polysulfide used may be obtained byreacting one mole of a mixture of hydroxide and hydrosulfide of alkalimetal, or of sulfide of alkali metal with 1 to 7 moles, preferably 1 to2 moles of sulfur beforehand according to the conventional process, ormay be obtained by reacting the above reactants in the presence ofaminocarbonyl-substituted halogenopyridine compound (hereinafterreferred to as ACHP) having the general formula (VII) to be prepared inthe reaction system and to be directly used in situ. Examples of thealkali metal for the hydroxide, hydrosulfide or sulfide of alkali metalinclude, lithium, sodium, potassium and the like, sodium beingpreferred. The amount of the hydroxide, hydro-sulfide or sulfide to beused is respectively 0.75 to 5 moles, preferably 1 to 1.5 moles per onemole of ACHP. In this reaction, normally water is used as a solvent, butorganic solvent may also be used so long as it is miscible withpolysulfide and water. Examples of the organic solvent include loweralcohol such as methanol, ethanol, propanol and the like, polyalcoholsuch as ethylene glycol, propylene glycol and the like: ethers such astetrahydrofuran: an aprotic polar solvent such as dioxane,dimethylsulfoxide and the like: ketones such as methyl ethyl ketone:nitriles such as acetonitrile: and the like. The amount of the solventused is normally 10 to 1000% by weight, preferably 10 to 100% by weightrelative to the weight of ACHP. Other reaction conditions in thisreaction may not generally be defined, but the reaction temperature isnormally 0° C. to a reflux temperature, preferably 80 to 150° C., thereaction pressure is atmospheric pressure to several atms., and thereaction time is generally 0.t to 30 hours.

The alkali metal salt of pyridine carboxylic acid amide (poly)sulfidehaving the general formula (VIII). which is obtained in the abovereaction is applicable to the following oxidation reaction as it is.

5. Oxidation Reaction

The oxidation reaction may be carried out in the same manner as in theoxidation reaction of the above process [A].

The ACPS or alkali metal salts thereof, which are obtained according tothis reaction, may easily be lead to APCA by an amination reactionexplained below or the above salt conversion reaction - anoxidation.condensation reaction explained below.

Typical examples of ACPS or salts thereof in the present invention,which are obtained according to the above processes [A] and [B], areshown in Table 1 as follows: ##STR9## or salts thereof.

                                      TABLE 1                                     __________________________________________________________________________    General formula (I) or salts thereof                                                Substituted                                                                   position of                                                              No.Compound                                                                         ##STR10##                                                                            R.sub.3                                                                          R.sub.4                                                                          SO.sub.2 Hposition ofSubstituted                                                    Kinds of Salts                                                                       melting point (°C.)Physical                                           Properties-                                   __________________________________________________________________________     8    3      CH.sub.3                                                                         CH.sub.3                                                                         2     --     --                                             9    "      "  "  "     Na salt                                                                              260-265                                                                       (decomposed)                                  10    "      "  "  "     NH.sub.4 salt                                                                        128-130                                       11    "      H  "  "     Na salt                                                                              --                                            12    "      "  C.sub.3 H.sub.7                                                                  "     "      --                                                            (iso)                                                         13    "      C.sub.2 H.sub.5                                                                  C.sub.2 H.sub.5                                                                  "     triethyl amine                                                                       --                                                                     salt                                                 14    "      CH.sub.3                                                                         CH.sub. 3                                                                        4     Ca salt                                                                              --                                            15    "      "  "  2     K salt --                                            __________________________________________________________________________

Next, the MPCA having the general formula (VI) and used as a startingmaterial in the above process [A] may be prepared according to thefollowing process: ##STR11## wherein R₃, R₄, Haλ, M', x and y are asdefined above.

The above polysulfidation reaction and acid treatment are explained morein detail.

6. Polysulfication Reaction

The polysulfication reaction may be carried out in the same manner as inthe polysulfidation reaction of the above process [B].

7. Acid Treatment

The conventional acid treatment of a reaction product obtained accordingto the above polysulfidation reaction and containing an alkali salt ofpyridinecarboxylic acid amide (poly)sulfide having the general formula(VIII) results in liberating the intended MPCA, evolving hydrogensulfide gas, and in generating sulfur. The acid treatment is carried outby adding a mineral acid having no oxidative action, for example,concentrated hydrochloric acid, dilute sulfuric acid or the like, to thereaction product so that pH may show 3 or less, followed by conventionalpurification and separation procedures to isolate the intended MPCA.

Further the ACPS or salts thereof in the present invention may be leadto aminosulfonyl-substituted pyridinecarboxylic acid amide compound(APCA) having the following general formula (IX) by the followingamination reaction or oxidation.condensation reaction: ##STR12## whereR₃ and R₄ are as defined above.

8. Animation Reaction

The amination reaction is carried out by dissolving or suspending theabove ACPS or salts thereof in a solvent such as water and addingthereto hydroxylamine-o-sulfonic acid compounds, or by addinghydroxylamine-o-sulfonic acid compounds to the reaction product obtainedaccording to the above oxidation reaction for-reacting. Preferably, abasic substance is further added in the above reaction. The order ofaddition of the hydroxylamine-o-sulfonic acid compounds and of the basicsubstance is not specifically limited, but it is preferred to first addthe hydroxylsmine-o-sulfonic acid compounds and then add the basicsubstance. Examples of hydroxylamine-o-sulfonic acid compounds includehydroxylamine-o-sulfonic acid, o-mesitylene sulfonylhydroxylamine andthe like, hydroxylamine-o-sulfonic acid being preferred. The amount ofthe hydroxylamine-o-sulfonic acid compounds used is 1 to 3 moles per onemole of ACPS or salts thereof. Examples of the basic substance includesodium acetate, sodium carbonate, potassium carbonate, sodiumhydrogencarbonate sodium phosphate, disodium hydrogenphosphate, sodiumhydroxide potassium hydroxide, ammonia, triethylamine and the like,ammonia, sodium acetate and sodium hydroxide being preferred. The amountof the basic substance used is 0.5 to 4 reacting equivalents per onereacting equivalent of ACPS or salts thereof. The reaction temperatureis not generally defined, but is normally 0 to 100° C., and the reactiontime is generally 10 minutes to 24 hours.

The reaction product may be subjected to the conventional purificationand separation procedures to obtain APCA. ##STR13## where R₃ and R₄ areas defined above.

9. Oxidation.Condensation Reaction

The oxidation condensation reaction is carried out by dissolving orsuspending ammonium salt of ACPS in a solvent such as water and addingthereto hypochlorite or halogen, or by adding hypochlorite or halogen tothe reaction product obtained according to the above oxidation or saltconversion reaction and containing ammonium salt of ACPS for reacting.Examples of hypochlorite include sodium hypochlorite, potassiumhypochlorite, calcium hypochlorite and the like, and examples of halogeninclude bromine, chlorine, iodine and the like, sodium hypochloritebeing preferred. The amount to be used of the hypochlorite or halogen is1 to 4 moles per one mole of ammonium salt of ACPS. The reactiontemperature is not generally defined, but is normally -10 to +50° C.,and the reaction time is generally 10 to 60 minutes.

The reaction product may be subjected to neutralization followed by theconventional purification and separation procedures to obtain APCA.

In the above process [b-2]. addition of an acid makes it possible toincrease yield. The acid may be added at any tim®during a time periodfrom the MPCA ammonium salt formation reaction step or the reaction stepof salt conversion to ammonium salt of ACPS to theoxidation.condensation reaction step, for example, between after theMPCA ammonium salt formation reaction and before the oxidation reaction,between after the oxidation reaction of ammonium salt of MPCA and beforethe oxidation, condensation reaction, or the like. Examples of the acidinclude inorganic acid or organic acid such as sulfuric acid,hydrochloric acid, nitric acid, phosphoric acid, acetic acid or thelike, sulfuric acid being preferred. The amount of the acid used isnormally 1 to 5 moles per one mole of respective reaction products inthe MPCA ammonium salt formation reaction, the salt conversion reactionto ammonium salt of ACPS, the oxidation reaction, or in the oxidationcondensation reaction.

The APCA obtained according to the above reaction may easily be lead toa substituted pyridinesulfonamide compound such asN-[(4,6-dimethoxypyrimidine-2-yl)aminocarbonyl]-3-dimethylamino-carbonyl-2-pyridine-sulfonamideand salts thereof, which are useful as herbicide for use in the cornfield as disclosed, for example, in European Patent ApplicationLaid-Open No. 232,067.

C. Examples

Examples, which are not to give any limitations to the process of thepresent invention, are shown below in order to describe more in detailthe process of the present invention.

Examples 1-8 demonstrate processes for production of novelmercapto-substituted pyridine compounds, and Examples 9-16 demonstrateprocesses for production of novel aminocarbonyl-substituted pyridinesulfinic acids.

Explanations are given for compounds of the present invention as well aspreparation examples of pyridine sulfonamide compound.

1. Example 1 (a) Synthetic Reaction of Pyridinepolysulfide

A mixture of 25.0 g (0.1 mole) of 96% sodium sulfide nona hydrate. 10.4g (0.325 mole) of sulfur and 56 mλ of water is refluxed by heating. Atthe time when sulfur dissolves completely to form a homogeneoussolution. 18.45 g (0.1 mole) of 2-chloro-N,N-dimethylnicotinamide isadded, followed by refluxing by heating for 18 hours to form sodium saltof N,N-dimethylnicotinamide-2-polysulfide.

(b) Acid Treatment

The above reaction product is allowed to cool down to room temperature,15 mλ of concentrated hydrochloric acid is carefully dropped(accompanying generation of hydrogen sulfide and precipitation ofsulfur). and after the completion of dropping, agitation is carried outfor 15 minutes. Sulfur is filtered off and washed with warm water, andthe filtrate and washing liquor are confirmed to be evaporated todryness under vacuum. The residue is repeatedly extracted withchloroform and dried over anhydrous solution sulfate, and chloroform isdistilled off and the residual- substance is purified with a silica gelcolumn chromatography (developing solvent: methanol/chloroform=1/9) toobtain 17.2 g of a yellow crystallineN,N-dimethyl-2-mercaptonicotinamide (m.p. 214-215° C).

2. Example 2 (a) Synthetic Reaction of Pyridinepolysulfide

A mixture of 5.25 g (0.021 mole) of 96% sodium sulfide nona hydrate. 2.2g (0.069 mole) of sulfur and 5 mλ of water is refluxed by heating. ATthe time when the sulfur dissolves completely to form a homogeneoussolution. 4.46 g (0.021 mole) of 2-chloro-N,N-diethylnicotinamide isadded, followed by being refluxed by heating for 10 hours to form asodium salt of N,N-diethylnicotinamide-2-polysulfide.

(b) Acid Treatment

After the above reaction product is allowed to cool down to roomtemperature, 4 mλ of concentrated hydrochloric acid is carefully dropped(accompanying generation of hydrogen sulfide and precipitation ofsulfur). After the completion of dropping procedure, agitation isfurther carried out for 15 minutes. The aqueous phase is extracted withdichloromethane, followed by drying and distilling off the solvent undervacuum and purification of the residue with a silica gel columnchromatography (developing solvent: methanol/chloroform=1/19) to obtain4.09 g of a yellow crystalline N,N-diethyl-2-mercaptonicotinamide (m.p.207-210° C).

3. Example 3 (a) Synthetic Reaction of Pyridinepolysulfide

A mixture of 24 g (0.3 mole) of sodium hydrosulfide of 70% purity. 9.6 g(0.3 mole) of sulfur. 12 g (0.3 mole) of sodium hydroxide and 15 mλ ofwater is refluxed by heating. At the time when the sulfur dissolvescompletely to form a homogeneous solution, 55.4 g (0.3 mole) of2-chloro-N,N-dimethyl-nicotinamide is added, followed by being refluxed(125° C.) by heating for 2 hours to form a sodium salt ofN,N-dimethylnicotinamide-2-polysulfide.

(b) Acid Treatment

After the above reaction product is allowed to cool down to roomtemperature, 150 mλ of water is added and about 30 mλ of concentratedhydrochloric acid is dropped so as to adjust to pH 2. while hydrogensulfide generates and sulfur precipitates. After the completion ofdropping, agitation is carried out at 60 to 70° C. for 30 minutes,followed by filtering off the sulfur while warming and by washing theresidue with 150 mλ of warm water to obtain filtrate and washing liquorwhich contain N,N-dimethyl-2-mercapto-nicotinamide.

(c) Oxidation and Bromination Reaction

The above mixture of filtrate and washing liquor is cooled with amixture of sodium chloride and ice, 147 g (0.92 mole) of bromine isdropped with stirring at 5° C. or lower. 100 mλ of a cold water is thencharged to be stirred, at -5° C. for 1 hour. The reaction product isextracted with 700 mλ of cold methylene chloride to obtain an extractliquor containing 2-bromosulfonyl-N,N-dimethylnicotinamide.

4. Example 4

The oxidation and bromination reaction in Example 4 is varied asfollows. Into 300 mλ of water is suspended 54.6 g (0.3 mole) ofN,N-dimethyl-2-mercaptonicotinamide to be cooled with agitation, and 144g (0.9 mole) of bromine is dropped at -6° C. to 0° C. After thecompletion of dropping above, purification procedure is carried out inthe same manner as in to obtain a methylene chloride solution containing2-bromosulfonyl-N.N-dimethylnicotinamide. The methylene chloridesolution is washed with 300 mλ of ice water and 200 mλ of cooled 1%aqueous solution of sodium thiosulfate, methylene chloride is distilledoff at an inner temperature of 30° C. or lower, followed by drying undervacuum to obtain 76 g of reaction product. The reaction product isdissolved in warm ethylene dichloride and is recrystallized withn-hexane to obtain 64 g (yield: 72.8%) of2-bromosulfonyl-N,N-dimethylnicotinamide (m.p. 108-111° C.).

5. Example 5 (a) Synthetic Reaction of Pyridinepolysulfide

A mixture of 55.4 g of 2-chloro-N,N-dimethyl-nicotinamide 24 g of sodiumhydrosulfide of 70% purity. 9.6 g of sulfur. 12 g of sodium hydroxideand 15 mλ of water is refluxed by heating with agitation for about 2hours to form a sodium salt of N,N-dimethylnicotinamide-2-polysulfide.

(b) Acid Treatment

To the above reaction product are added 150 mλ of water and 30 mλ of a50% aqueous sulfuric acid solution to be stirred at 60 to 70° C. for 30minutes, and the precipitated sulfur is filtered off with warming. Thesulfur is washed with 100 warm water, and the filtrate and washingliquor are combined to obtain a solution containingN,N-dimethyl-2-mercaptonicotinamide.

(c) Oxidation and Bromination

The above solution is cooled down to 0° C. or lower. 350 mλ of methylenechloride is added. 144 g of bromine is dropped over about 20 minutes anda methylene chloride layer is separated to obtain a methylene chloridesolution of 2-bromosulfonyl-N,N-dimethylnicotinamide.

6. Example 6 (a) N-oxidation Reaction

One hundred grams of 2-chloro-N,N-dimethylnicotinamide is dissolved in100 mλ of trifluoroacetic acid to be heated at 80 to 90° C., 240 g of30% hydrogen peroxide water is dropped over about 1 hour, and 200 mλ oftrifluoroacetic acid is added to be reacted for 2 hours.

After the completion of the reaction, the water and trifluoroacetic acidin the reaction mixture are distilled off under vacuum, followed bypurification with a silica gel column chromatography to obtain 56.7 g of2-chloro-N,N-dimethylnicotinamide-1-oxide (n²³ _(D).sup..1: 1.5822) of98% purity and 50.0 g of that of purity 85%.

(b) Synthetic Reaction of Pyridinepolysulfide and Acid Treatment

A mixture of 13.3 g of sodium sulfide nona hydrate, 1.6 g of sulfur and10 mλ of water is heated and dissolved to prepare sodium salt ofpolysulfide beforehand. Thereto is added 10 g of the98%purity2-chloro-N,N-dimethylnicotinamide-1-oxideobtained in the above (a)to be reacted at 95° C. for 2 hours.

After the completion of the reaction, 30 mλ of water and 10 mλ ofconcentrated hydrochloric acid are added to the reaction mixture toprecipitate sulfur, followed by filtering with warming, washing thesulfur with about 50 mλ of warm water, and by combining the filtrate andwashing liquor to obtain 120 mλ of an aqueous solution ofN,N-dimethyl-2-mercaptonicotinamide-1-oxide a melting point of which is115.5 to 118° C.

(c) Oxidation and Chlorination Reaction

One hundred and twenty milliliter of the aqueous solution ofN,N-dimethyl-2-mercaptonicotinamide-1-oxide obtained in the above (b) iscooled to 0 to 5° C. and is subjected to reaction while introducingchlorine gas until it is not absorbed any more.

After the completion of the reaction, the reaction mixture is subjectedto air buffling to remove excess chlorine, 60 mλ of methylene chlorideand 60 mλ of water are then added for extraction, resulting in obtaining65 mλ of a methylene chloride solution of2-chlorosulfonyl-N,N-dimethylnicotinamide-1-oxide, a melting point ofwhich is 96.5 to 100° C.

(d) Amidation

Into 65 mλ of the methylene chloride solution of2-chlorosulfonyl-N,N-dimethylnicotinamide-1-oxide obtained in the above(c) is dropped 10 g of a 28% ammonia water to be reacted.

After the completion of the reaction, the reaction mixture isneutralized with concentrated hydrochloric acid, and the resultingcrystallines are filtered and dried to obtain 8.0 g of2-aminosulfonyl-N,N-dimethylnicotinamide-1-oxide (m.p.: 213-215° C.).

(a) Synthetic Reaction of Pyridinepolysulfide

A mixture of 26.4 g (0.105 mole) of 96% sodium sulfide nona hydrate.10.8 g (0.338 mole) of sulfur and 56 mλ of water is refluxed by heating.At the time when a homogeneous solution is formed. 18.45 g (0.1 mole) of2-chloro-N,N-dimethylnicotinamide is added, followed by refluxing byheating for 20 hours to form a sodium salt ofN,N-dimethyl-nicotinamide-2-polysulfide.

(b) Acid Treatment

The above reaction product is allowed to cool down to room temperature.15 mλ of concentrated hydrochloric acid is then carefully dropped. Afterthe completion of dropping, stirring is carried out for 15 minutes toform N,N-dimethyl-2-mercaptonicotinamide.

(c) Oxidation and Chlorination Reaction

The resulting insoluble matter is filtered off and washed with warmwater, the filtrate and washing liquor are combined, about 50 mλ ofdichloromethane is added to the combined filtrate and washing liquor tobe ice-cooled, and chlorine gas is introduced thereinto. Afterconfirming disappearance of N,N-dimethyl-2-mercaptonicotinamide,introduction of chlorine gas is stopped to form2-chlorosulfonyl-N,N-dimethylnicotinamide (m.p. 114-117° C.). Thereaction mixture is charged into ice water, the dichloromethane layer isseparated and collected, the collected dichloromethane layer is combinedwith one obtained by extracting the water layer with dichloromethane tobe washed with water, followed by drying over anhydrous sodium sulfateand by cooling with ice water again.

(d) Amidation Reaction

Ammonia gas is introduced into the resulting dichloromethane layer at10° C. or lower. At the time when the reaction mixture becomes weaklyalkaline, introduction of ammonia gas is stopped. Dichloromethane isdistilled off the reaction product, the remaining white crystals arewashed with ethyl acetate followed by water, and dried to obtain 15.5 gof 2-aminosulfonyl-N,N-dimethylnicotinamide (m.p. 209-211° C.).

(e) Condensation

A mixed solution containing 250 mg of 2-amino-4.6-dimethoxypyrimidine,0.65 g of triethylamine and 2.5 g of ethyl acetate is dropped at 15° C.into 6.3 g of an ethyl acetate solution of 20% phosgene to be reactedfor 1 hour keeping the temperature at 15° C. followed by warming in anoil bath at 90° C. to distill off excessive phosgene and ethyl acetate,adding a solution prepared by dissolving 300 mg of2-aminosulfonyl-N,N-dimethylnicotinamide in 10 mλ of acetonitrile, andby dropping 0.2 g of triethylamine to be reacted for 1 hour at roomtemperature.

After the completion of the reaction, the reaction product is chargedinto water, followed by acidifying with hydrochloric acid, filtering offdeposited crystals, washing with water, and by drying to obtain 0.46 gofN-[(4,6-dimethoxypyrimidine-2-yl)aminocarbonyl]-3-dimethyl-aminocarbonyl-2-pyridinesulfonamide (m.p. 169-173° C.).

8. Example 8

A field soil is packed in a 1/1.500 are pot, and seeds of various kindsof plants are sowed thereon. When respective plants reach certain plantstages in leaf number, respectively, (corn:3.2 leaf stage, wheat:3.5leaf stage, common cocklebur: 2.5 leaf stage, tall morning glory:1.0leaf stage, smartweed: 1.2 leaf stage, prickly sida:1.0 leaf stage,slender amaranth: 0.5 leaf stage, barnyard grass:2.0 leaf stage), awettable powder ofN-[(4,6-dimethoxypyrimidine-2-yl)aminocarbonyl]-3-dimethylaminocarbonyl-2-pyridinesulfonamideis weighed by such an amount as to be 1.25 (g/a) (as an amount of theactive ingredient) to be diluted with 5L of water per one acre, followedby adding to the aqueous solution, an agricultural spreader by such anamount as to be 0.2% to be subjected to foliar application with asmall-sized sprayer. Twenty four days after application, growthconditions of respective plants are observed visually and a degree ofgrowth control is evaluated by ten grades (1 : the same as innon-application area to 10 : complete control). The results are shownbelow.

    ______________________________________                                                        Degree of                                                     Plants          Growth Control                                                ______________________________________                                        Corn            1                                                             Wheat           8                                                             Common cocklebur                                                                              10                                                            Tall morning glory                                                                            8                                                             Prickly sida    7                                                             Smartweed       8                                                             Slender amaranth                                                                              10                                                            Barnyard grass  10                                                            ______________________________________                                    

9. Example 9 Preparation of the starting material, MPCA (a)Polysulfidation Reaction and Acid Treatment

A mixture of 55.4 g of 2-chloro-N,N-dimethylnicotinamide. 24 g of 70%purity sodium hydrosulfide. 96 g of sulfur. 12 g of sodium hydroxide and15 mλ of water is refluxed for about 2 hours by heating with agitationto form sodium salt of N,N-dimethyl-nicotinamide-2-polysulfide. To theabove product are added 150 mλ of water and 30 mλ of a 50% aqueoussulfuric acid solution under stirring for 30 minutes at 60 to 70° C.,and the generated sulfur is filtered off with warming. The sulfur iswashed with 100 mλ of warm water, and the filtrate and the washingliquor are combined together to obtain a solution containing2-mercapto-N,N-dimethylnicotinamide. The solution is cooled down to 10°C., and deposited crystals are collected by filtration. Further, thefiltrate is thickened to such an extent that the volume is reduced toabout 1/3, and the deposited crystals are collected by filtration. Thesecrystals are combined and dried to obtain 46.5 g of2-mercapto-N,N-dimethylnicotinamide having a melting point of 200 to208° C.

Preparation of ACPS salt of the present invention (b) Salt Formation

A 300 mλ four-necked flask equipped with thermometer, dropping funneland stirrer is charged with 18.2 g (0.1 mole) of2-mercapto-N,N-dimethylnicotinamide. 4.4 g (0.11 mole) of sodiumhydroxide and 50 mλ of water to be dissolved with agitation for beingreacted at room temperature for 10 minutes to obtain a reaction productcontaining sodium-N,N-dimethylnicotinamide-2-thiolate.

Separately, the same reaction as above is carried out to obtain areaction product. The reaction product is thickened, and the depositedcrystals are filtered off and dried to isolate 20.0 g ofsodium-N,N-dimethylnicotinamide-2-thiolate having a melting point of 260to 268° C. (a little decomposed).

(c) Oxidation Reaction

Into the reaction product obtained according to the above salt formationreaction is dropped with agitation for about 30 minutes 22.7 g (0.2mole) of 30% aqueous hydrogen peroxide solution at a temperature of 10to 20° C. externally cooling for reacting to obtain a reaction productcontaining sodium N,N-dimethylnicotinamide-2-sulfinate.

Separately, the salt formation reaction and oxidation reaction iscarried out in the same manner as above to obtain a reaction product.The reaction product is thickened and dried to isolate 22.0 g of sodiumN,N-dimethylnicotinamide-2-sulfinate (yield based on MPCA: 93.2%) havinga melting point of 260 to 265° C. (colored brown, decomposed).

(d) Salt Conversion Reaction

To the reaction product obtained according to the above oxidationreaction as it is, is added 60.7 g (1.0 mole) of 28% ammonia water, and12.3 g (0.125 mole) of concentrated sulfuric acid at a temperature of 10to 20° C. is then dropped thereinto with agitation for 15 minutes forreacting to obtain a reaction product containing ammonium salt ofN,N-dimethyl-nicotinamide-2-sulfinic acid.

Separately, the salt formation reaction, oxidation reaction and the saltconversion reaction are carried out in the same manner as above toobtain a reaction product. The reaction product is thickened and dried,and the residue is extracted with methanol and the extract liquor isdried to isolate 20.9 g of ammonium salt ofN,N-dimethylnicotinamide-2-sulfinic acid (yield based on MPCA: 90.5%)having a melting point of 128 to 130° C.

Referential Example 1 Preparation of AFCA: (Oxidation, CondensationReaction)

Into the reaction product obtained according to the salt conversionreaction in Example 10, as it is. ,s dropped with agitation for about 30minutes 32 g (0.2 mole) of bromine at a temperature of 10 to 20° C. forreacting, followed by stirring for 30 minutes and neutralizing withconcentrated sulfuric acid to pH 3-6 to deposit white crystals. Thisreaction product is cooled down to about 20° C. and is then filtered,washed with water and dried to obtain 16.2 g (yield based on MPCA:70.7%: purity: 96.5%) of 2-aminosulfonyl-N,N-dimethylnicotinamide.

10. Example 10 Preparation of ACPS salt of the present invention (a)Salt Formation Reaction

A 300 mλ four-necked flask equipped with thermometer, dropping funneland stirrer is charged with 9.1 g (0.05 mole) of2-mercapto-N,N-dimethylnicotinamide and 45.5 of 28% ammonia water,followed by dissolving with agitation and by reacting for 10 minutes atroom temperature to obtain a reaction product containingammonium-N,N-dimethylnicotinamide-2-thiolate.

The ammonium-N,N-dimethylnicotinamide-2-thiolate (9.7 g) has a meltingpoint of 198 to 201° C. (partly decomposed).

(b) Oxidation Reaction

Into the reaction product obtained according to the above salt formationreaction, as it is, is dropped with agitation for about 15 minutes 11.4g (0.10 mole) of 30% aqueous hydrogen peroxide solution at a temperatureof 5 to 20° C. externally cooling for reacting, followed by droppingthereinto with agitation for about 20 minutes 12.5 g (0.125 mole) ofconcentrated sulfuric acid at a temperature of 5 to 20° C. to obtain areaction product containing ammonium salt ofN,N-dimethylnicotinamide-2-sulfinic acid.

Separately, the ammonium salt formation reaction and oxidation reactionis carried out in the same manner as above to obtain a reaction product.The reaction product is thickened and dried, and the residue isextracted with methanol, followed by drying the extract liquor toisolate 10.8 g (yield based on MPCA: 93.5%) of ammonium salt ofN,N-dimethylnicotinamide-2-sulfinic acid having a melting point of 128to 130° C.

Referential Example 2 Preparation of APCA: (Oxidation·CondensationReaction)

Into the reaction product obtained according to the oxidation theoxidation reaction in Example 11. as it is, is dropped with-agitationfor about 30 minutes 62 g (0.1 mole) of 12% sodium hypochlorite solutionat a temperature of 5 to 20° C. for reacting, followed by neutralizingwith concentrated sulfuric acid to pH 3-6 to deposit white crystals.This reaction product is cooled down to about 20° C., followed byfiltering, washing with water and by drying to obtain 8.5 g (yield basedon MPCA: 74.2%: purity: 95.6%) of2-aminosulfonyl-N,N-dimethylnicotinamide.

11. Example 11

Procedures of Example 11 are repeated except that dropping of 12.5 g(0.125 mole) of concentrated sulfuric acid after the completion of theoxidation reaction is replaced by dropping of 24.5 g (0.125 mole) of 50%sulfuric acid to obtain 10.5 g (yield based on MPCA: 90.9%) of ammoniumsalt of N,N-dimethylnicotin-amide-2-sulfinic acid.

Referential Example 3

Procedures of Referential Example 2 are repeated except that thereaction product obtained according to the oxidation reaction in Example12 is used as it is and 62 g of 12% sodium hypochlorite solution isreplaced by 28 g (0.175 mole) of bromine to obtain 6.98 g (yield basedon MPCA: 61.0%: purity: 98.6%) of2-aminosulfonyl-N,N-dimethylnicotinamide.

12. Example 12

Procedures of Example 11 are repeated except that a step of droppingthereinto with agitation for about 20 minutes 12.5 g (0.125 mole) ofconcentrated sulfuric acid at a temperature of 5 to 20° C. after thecompletion of the oxidation reaction, is carried out between after thecompletion of the salt formation reaction and before the oxidationreaction to obtain 10.3 g (yield based on MPCA: 89.2%) of ammonium saltof N,N-dimethyl-nicotinamide-2-sulfinic acid.

Referential Example 4

The reaction product obtained according to the oxidation reaction in-Example 13 is used as it is, and procedures of Referential Example 2are repeated to obtain 6.8% g (yield based on MPCA: 59.6%: purity:93.8%) of 2-aminosulfonyl-N,N-dimethylnicotinamide.

13. Example 13 Preparation of ACPS salt of the present invention SaltFormation Reaction

A 300 mλ four-necked flask equipped with thermometer, dropping funneland stirrer is charged with 5.0 g (0.0275 mole) of2-mercapto-N,N-dimethylnicotinamide. 1.2 g (0.03 mole) of sodiumhydroxide and 15 mλ of water, followed by dissolving with agitation andby reacting at room temperature for 10 minutes to obtain a reactionproduct containing sodium-N,N-dimethylnicotin-amide-2-thiolate.

Separately, a reaction product obtained by carrying out the samereaction as above is thickened, and the deposited crystals are filteredoff and dried to isolate 5.53 g ofsodium-N,N-dimethylnicotinamide-2-thiolate having a melting point of 260to 268° C. (a little decomposed).

(b) Oxidation Reaction

Into the reaction product obtained according to the above salt formationreaction, as it is.,is dropped with agitation for about 30 minutes 6.23g (0.055 mole) of 30% aqueous hydrogen peroxide solution at atemperature of 10 to 20° C. externally cooling for reacting to obtain areaction product containing sodium N,N-dimethylnicotinamide-2-sulfinate.

Separately, a reaction product obtained by carrying out the saltformation reaction and oxidation reaction in the same manner as above isthickened and dried to isolate 6.05 g (yield based on MPCA: 93.2%) ofsodium N,N-dimethylnicotinamide-2-sulfinate having a melting point of260 to 265° C. (colored brown, decomposed).

Referential Example 5 Preparation of APCA: (Amination Reaction)

To the reaction product obtained according to the oxidation reaction inExample 14. as it is, is added 2.48 g (0.03 mole) of sodium acetate at atemperature of 10 to 30° C., and 4.03 g (0.0357 mole) ofhydroxylamine-o-sulfonic acid is then added for reacting with agitationfor about 5 hours. Crystals deposited at about 20° C. is filtered,washed with water and dried to obtain 4.56 g (yield based on MPCA:72.4%: purity: 95.3%) of 2-aminosulfonyl-N,N-dimethylnicotinamide.

Referential Example 6

Procedures of Referential Example 14 are repeated except that 1.83 g(0.03 mole) of 28% ammonia water in place of 2.48 g of sodium acetate isused and that the reaction time is 3 hours in place of 5 hours to obtain4.66 g (yield based on MPCA: 74.0%: purity: 98.2%) of2-aminosulfonyl-N,N-dimethylnicotinamide.

Referential Example 7

Procedures of Referential Example 5 are repeated except that 4.16 g(0.0412 mole) of triethylamine in place of 2.48 g of sodium acetate isused and that the reaction time is 3 hours in place of 5 hours to obtain4.35 g (yield based on MPCA: 69.1%: purity: 97.1%) of2-aminosulfonyl-N,N-dimethylnicotinamide.

14. Example 14

Procedures of Example 14 are repeated except that 15 mλ of water used inthe salt formation reaction of Example 5 is replaced by 7.5 mλ thereofto obtain 6.08 g (yield based on MPCA: 93.7%) of sodiumN,N-dimethylnicotinamide-w-sulfinate.

Referential Example 8

Procedures of Referential Example 5 are repeated except that thereaction product obtained according to the oxidation reaction of Example15 is used as it is, that a step of adding 2.48 g of sodium acetatefollowed by adding 4.03 g of hydroxylamine-o-sulfonic acid is replacedby a step of adding 4.03 g (0.0357 mole) of hydroxylamine-o-sulfonicacid followed by adding 1.83 g (0.03 mole) of 28% ammonia water, andthat the reaction time is 3 hours in place of 5 hours to obtain 4.77 g(yield based on MPCA: 75.8%: purity: 98.3%) of2-aminosulfonyl-N,N-dimethylnicotinamide.

15. Example 15

Procedures of Example 14 are repeated except that 1.8 g (0.03 mole) of28% ammonia water in place of 1.2 g of sodium hydroxide is used toobtain 5.90 g (yield based on MPCA: 92.9%) of ammonium salt ofN,N-dimethylnicotinamide-2-sulfinic acid.

Referential Example 9

Procedures of Referential Example 5 are repeated except that thereaction product obtained according to the oxidation reaction of Example16 is used as it is, and that the reaction time is 6 hours in place of 5hours to obtain 4.68 g (yield based on MPCA: 74.3%: purity: 98.0%) of2-aminosulfonyl-N,N-dimethylnicotinamide.

16. Example 16 Preparation of ACPS salt of the present invention (a)Polysulfidation Reaction

A mixture of 55.4 g of 2-chloro-N,N-dimethylnicotinamide, 24 g of 70%purity sodium hydrosulfide. 96. g of sulfur. 12 g of sodium hydroxideand 15 mλ of water is refluxed by heating with agitation for about 2hours to obtain a reaction product containing 68.7 g of sodium salt ofN,N-dimethylnicotinamide-2-(poly)sulfide.

(b) Oxidation Reaction

To the reaction product obtained according to the above polysulfidationreaction in Example 8 are added 180 mλ of water and 18 g of a 40%aqueous sodium hydroxide solution, followed by dropping thereinto withagitation for 30 minutes 75.8 g (0.78 mole) of 35% aqueous hydrogenperoxide solution at a temperature of 10 to 20° C. for reacting toobtain a reaction product containing sodiumN,N-dimethylnicotinamide-2-sulfinate.

The reaction product thus obtained is subjected to filtration to filteroff free sulfur, and the sulfur is washed with water to obtain filtrateand washing liquor.

Separately, polysulfidation reaction and oxidation reaction are carriedout in the same manner as above to obtain a reaction product. Similarlyfree sulfur is removed from the reaction product, followed by thickeningand drying to isolate 65.0 g (yield based on ACHP: 91.8%) of sodiumN,N-dimethylnicotinamide-2-sulfinate having a melting point of 258 to265° C. (colored brown, decomposed).

Referential Example 10 Preparation of APCA: (Amination Reaction)

To a combined solution of the filtrate and the washing liquor obtainedaccording to the oxidation reaction in Example 8 is added 54.24 g (0.48mole) of hydroxylamine-o-sulfonic acid with agitation at 10° C. or lowerto be dissolved, and 48 g (0.48 mole) of 40% aqueous sodium hydroxidesolution is then dropped thereinto to be reacted with agitation for 3hours at a temperature of 10 to 20° C.

A reaction product thus obtained is filtered to obtain crystals, whichare washed with water and dried to obtain 52.5 g (yield based on ACHP:76.4%: purity: 96.5%) of 2-aminosulfonyl-N,N-dimethylnicotinamide.

What is claimed is:
 1. An aminocarbonyl-substituted pyridinesulfinicacid, having formula (V"): ##STR14## wherein R₃ and R₄ are independentlyselected from the group consisting of a hydrogen atom and an alkylgroup, or a salt thereof.
 2. An aminocarbonyl-substitutedpyridinesulfinic acid having the formula: ##STR15## wherein R₃ isindependently selected from the group consisting of a hydrogen and analkyl group, or a salt thereof.
 3. A compound thereof as claimed inclaim 1, wherein said aminocarbonyl-substituted pyridinesulfinic acid orsalt thereof is N,N-dimethylnicotinamide-2-sulfinic acid, sodium saltthereof or ammonium salt thereof.